Is EOMES p.Ser91Arg (c.271A>C) pathogenic?

EOMES p.Ser91Arg (c.271A>C) is classified Likely benign in EOMES (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-24). AlphaMissense: ambiguous (0.5037); Rare (popmax 0.926%, mid).

How common is EOMES p.Ser91Arg (c.271A>C) in the general population?

EOMES p.Ser91Arg (c.271A>C) is rare (popmax 0.926%, mid) (gnomAD).

What do computational predictors say about EOMES p.Ser91Arg (c.271A>C)?

AlphaMissense predicts ambiguous (score 0.5037) — an in-silico prediction, not a clinical call.

EOMES p.Ser91Arg

c.271A>C · rs529375594 · VCV718935

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5037 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.926%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5037	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -7.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 779 bp · p 0.00084 · regional, not allelic
Overall
CADD	18.06	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.926% Middle Eastern · 50/5,398 alleles

Filtering AF 0.722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.649%

Overall 0.156% 2,385/1,526,144 alleles · rare exomes 2,189/1,374,028 · genomes 196/152,116 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.926%	108
Ashkenazi Jewishnot grpmax-eligible	0.585%	171
South Asian	0.237%	422
Remaining individualsnot grpmax-eligible	0.207%	484
European (non-Finnish)	0.155%	644
Admixed American	0.0828%	1,208
African / African-American	0.0398%	2,515
Finnishnot grpmax-eligible	0.0335%	2,984
East Asian	0.00264%	37,872

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EOMES
Protein: p.Ser91Arg
Coding: c.271A>C
MANE Select: NM_001278182
dbSNP: rs529375594
Type: single nucleotide variant
Location: chr3:27722024 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 56.74

Full EOMES gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EOMES p.Tyr231Cys Uncertain significance ★★ ⚠ same type
EOMES p.Glu113= Likely benign ★★ same type
EOMES p.Pro641= Benign ★★ same type
EOMES p.Ser392= Likely benign ★★ same type
EOMES p.Ala118Pro Uncertain significance ★ ⚠ same type
EOMES p.Ala17Pro Uncertain significance ★ ⚠ same type
EOMES p.Ala206Gly Uncertain significance ★ ⚠ same type
EOMES p.Ala218Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/eomes-p-ser91arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown